Metabolic reprogramming of myeloid-derived suppressor cells in the context of organ transplantation.

ABSTRACT

Myeloid-derived suppressor cells (MDSCs) are naturally occurring leukocytes that develop from immature myeloid cells under inflammatory conditions that were discovered initially in the context of tumor immunity. Because of their robust immune inhibitory activities, there has been growing interest in MDSC-based cellular therapies for transplant tolerance induction. Indeed, various pre-clinical studies have introduced in vivo expansion or adoptive transfer of MDSC as a promising therapeutic strategy leading to a profound extension of allograft survival due to suppression of alloreactive T cells. However, several limitations of cellular therapies using MDSCs remain to be addressed, including their heterogeneous nature and limited expansion capacity. Metabolic reprogramming plays a crucial role for differentiation, proliferation and effector function of immune cells. Notably, recent reports have focused on a distinct metabolic phenotype underlying the differentiation of MDSCs in an inflammatory microenvironment representing a regulatory target. A better understanding of the metabolic reprogramming of MDSCs may thus provide novel insights for MDSC-based treatment approaches in transplantation. In this review, we will summarize recent, interdisciplinary findings on MDSCs metabolic reprogramming, dissect the underlying molecular mechanisms and discuss the relevance for potential treatment approaches in solid-organ transplantation.